Bottom Line:
Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin.Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity.However, the percentage of transdifferentiation was significantly higher than fusion.

ABSTRACTMSCs have become a popular target for developing end-stage liver therapies. In this study, two models of bone marrow chimeric mice were used to construct the liver failure models. Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity. However, the percentage of transdifferentiation was significantly higher than fusion. So it was considered that MSCs which transdifferentiated into hepatocyte-likes cells played important roles for repairing the injuring liver function.

fig3: MSCs migrated to the damaged liver and had the proliferative activity. (a) IF analysis of Ki-67 expression (red) to visualize primary hepatocyte cells indicated that some of the donor GFP+ MSCs (green) are overlapped. Nuclear DAPI (blue) staining was used as a counterstain. The images were then merged. Bar: 75 μm. Arrow was directed to the double positive cells. All the experiments were repeated three times, at least 3 samples were included in each group. (b) Quantitative data of the GFP and Ki67 positive cells in IHC of different days after injuring (***P < 0.001).

Mentions:
On days 14 and 21 after CCl4 injection, FISH and IF were used to detect Y-chromosome- and GFP-positive cells. As shown in Figure 2(a), expression of the Y chromosome and GFP could be detected in the same cells of the damaged liver using laser confocal microscopy, which suggests that MSCs can fuse with primary hepatocytes. The population of both Y-chromosome- and GFP-positive cells ranged from 0.32% to 0.87% (Figure 2(b)). In addition, we also detected GFP- and Ki67-positive cells with FISH and IF on days 3, 14, and 21. GFP and Ki67 were expressed in the same cells of the damaged liver, which suggests that the MSCs that migrated to the liver have proliferative activity (Figures 3(a) and 3(b)). Together, these results show that MSCs can fuse with hepatocytes and maintain proliferative activity.

fig3: MSCs migrated to the damaged liver and had the proliferative activity. (a) IF analysis of Ki-67 expression (red) to visualize primary hepatocyte cells indicated that some of the donor GFP+ MSCs (green) are overlapped. Nuclear DAPI (blue) staining was used as a counterstain. The images were then merged. Bar: 75 μm. Arrow was directed to the double positive cells. All the experiments were repeated three times, at least 3 samples were included in each group. (b) Quantitative data of the GFP and Ki67 positive cells in IHC of different days after injuring (***P < 0.001).

Mentions:
On days 14 and 21 after CCl4 injection, FISH and IF were used to detect Y-chromosome- and GFP-positive cells. As shown in Figure 2(a), expression of the Y chromosome and GFP could be detected in the same cells of the damaged liver using laser confocal microscopy, which suggests that MSCs can fuse with primary hepatocytes. The population of both Y-chromosome- and GFP-positive cells ranged from 0.32% to 0.87% (Figure 2(b)). In addition, we also detected GFP- and Ki67-positive cells with FISH and IF on days 3, 14, and 21. GFP and Ki67 were expressed in the same cells of the damaged liver, which suggests that the MSCs that migrated to the liver have proliferative activity (Figures 3(a) and 3(b)). Together, these results show that MSCs can fuse with hepatocytes and maintain proliferative activity.

Bottom Line:
Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin.Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity.However, the percentage of transdifferentiation was significantly higher than fusion.

ABSTRACTMSCs have become a popular target for developing end-stage liver therapies. In this study, two models of bone marrow chimeric mice were used to construct the liver failure models. Then it was found that MSCs can transdifferentiate into hepatocyte-like cells and these hepatocyte-like cells can significantly express albumin. Furthermore it was also found that MSCs can fuse with the hepatocytes and these cells had the proliferation activity. However, the percentage of transdifferentiation was significantly higher than fusion. So it was considered that MSCs which transdifferentiated into hepatocyte-likes cells played important roles for repairing the injuring liver function.